Investigating sexual health after breast cancer by longitudinal assessment of patient-reported outcomes.

BACKGROUND: Sexual concerns are a major unaddressed need among survivors of breast cancer (BC) with significant negative effects on quality of life. We longitudinally analyzed sexual health over time, using patient-reported outcomes. METHODS: Patients with stage I-III BC prospectively included from the CANcer TOxicity cohort (CANTO) provided data at diagnosis, then 1, 2, and 4 years afterward. Sexual concerns outcomes included poor body image (score ≤91/100), poor sexual functioning (≤16/100), poor sexual enjoyment (≤66/100), and sexual inactivity (EORTC QLQ-B23). Multivariate generalized estimating equation models assessed associations with sexual concerns after diagnosis, adjusting for age, sociodemographic, tumor, treatment, and clinical characteristics. RESULTS: Nearly 78.1% among 7895 patients reported at least one sexual concern between diagnosis and 4 years' follow-up. Over time, the proportion of patients reporting sexual concerns either increased or remained constant with diagnosis. Less than half (46%, range 11.4-57) of the patients with sexual concerns reported the use of supportive care strategies, including gynecological or psychological consultations (range 11.4-57.4). Factors consistently associated with sexual concerns up to 4 years after diagnosis included already reporting the same concern at diagnosis [odds ratio (OR)poor body image 3.48 [95% confidence interval (CI) 3.11-3.89]; ORsexual inactivity 9.94 (95% CI 8.84-11.18), ORpoor sexual function 9.75 (95% CI 8.67-10.95), ORpoorsexual enjoyment 3.96 (95% CI 3.34-4.69)], endocrine therapy use [ORpoor body image 1.15 (95% CI 1.01-1.31); ORsexual inactivity 1.19 (95% CI 1.02-1.39), ORpoor sexual function 1.17 (95% CI 1.01-1.37), ORpoor sexual enjoyment 1.23 (95% CI 1.00-1.53)], and depression [ORpoor body image 2.00 (95% CI 1.72-2.34); ORsexual inactivity 1.66 (95% CI 1.40-1.97), ORpoor sexual function 1.69 (95% CI 1.43-2.00), ORpoor sexual enjoyment 1.94 (95% CI 1.50-2.51)]. Outcome-specific associations were also identified. CONCLUSIONS: Sexual concerns seem frequent, persistent, and insufficiently addressed. Pretreatment concerns, endocrine therapy, and emotional distress are commonly associated factors. A proactive evaluation of sexual health across the care continuum is needed, to promptly identify patients suitable for multidisciplinary counseling, referral, and supportive interventions.

Factors associated with enrolment in clinical trials among women with early-stage breast cancer.

BACKGROUND: Clinical trials allow development of innovative treatments and ameliorate the quality of clinical care in oncology. Data show that only a minority of patients are enrolled in clinical trials. We assessed enrolment in clinical trials and its correlates among women with early breast cancer. METHODS: We included 9516 patients with stage I-III breast cancer from the multicenter, prospective CANTO study (NCT01993498), followed-up until year 4 (Y4) post-diagnosis. We assessed factors associated with enrolment using multivariable logistic regression. In exploratory, propensity score matched analyses, we used multiple linear regression to evaluate the relationship of enrolment in clinical trials with the European Organisation for Research and Treatment of Cancer Quality Of Life (QoL) questionnaire (EORTC QLQ-C30) Summary Score and described clinical outcomes (distant disease event, invasive disease event, and death by any cause) according to enrolment. RESULTS: Overall, 1716 patients (18%) were enrolled in a clinical trial until Y4 post-diagnosis of breast cancer. Socioeconomic factors were not associated with enrolment. Centres of intermediate volume were most likely to enrol patients in clinical trials [versus low volume, odds ratio 1.45 (95% confidence interval (CI) 1.08-1.95), P = 0.0124]. Among 2118 propensity score matched patients, enrolment was associated with better QoL at Y4 (adjusted mean difference versus not enrolled 1.37, 95% CI 0.03-2.71, P = 0.0458), and clinical outcomes (enrolled versus not enrolled, distant disease event 7.3% versus 10.1%, P = 0.0206; invasive disease event 8.2% versus 10.5%, P = 0.0732; death by any cause 2.8% versus 3.7%, P = 0.2707). CONCLUSIONS: In this large study, one in five patients enrolled on a clinical trial until Y4 after diagnosis of early breast cancer. Geographical and centre-related factors were significantly associated with enrolment in clinical trials. Inclusion in clinical trials seemed associated with improved QoL and clinical outcomes. Access to innovation for early-stage breast cancer patients should be encouraged and facilitated by overcoming organizational and geographical barriers to recruitment.

Highly favorable outcome in BRCA-mutated metastatic breast cancer patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

Breast cancer carrying BRCA mutation may be highly sensitive to DNA-damaging agents. We hypothesized a better outcome for BRCA-mutated (BRCA(mut)) metastatic breast cancer (MBC) patients receiving high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HDC AHSCT) versus unaffected BRCA (BRCA wild type; (BRCA(wt))) or patients without documented BRCA mutation (BRCA untested (BRCA(ut))). All female patients treated for MBC with AHSCT at Institut Paoli-Calmettes between 2003 and 2012 were included. BRCA(mut) and BRCA(wt) patients were identified from our institutional genetic database. Overall survival (OS) was the primary end point. A total of 235 patients were included. In all, 15 patients were BRCA(mut), 62 BRCA(wt) and 149 BRCA(ut). In multivariate analyses, the BRCA(mut) status was an independent prognostic factor for OS (hazard ratio (HR): 3.08, 95% confidence interval (CI): 1.10-8.64, P=0.0326) and PFS (HR: 2.52, 95% CI :1.29-4.91, P=0.0069). In this large series of MBC receiving HDC AHSCT, we report a highly favorable survival outcome in the subset of patients with documented germline BRCA mutations.

Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study.

BACKGROUND: Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations. METHODS: Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis. RESULTS: After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2-93.1), 92.8 % (95 % CI: 90.7-95) and 95.1 % (95 % CI, 93.3-96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS. CONCLUSIONS: Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment.

Buccodental side effects of sunitinib in patients with metastatic renal cell carcinoma.

BACKGROUND: Sunitinib is a tyrosine kinase inhibitor approved for the treatment of renal cell carcinoma (RCC). Few data evaluated severe buccodental adverse events. The aim of this study was to evaluate sunitinib buccodental toxicity in patients with metastatic RCC and to compare it with that of standard chemotherapy in patients with other solid cancers. METHODS: Patients with RCC treated with sunitinib and patients with other solid tumours treated with chemotherapy were followed for 3 months. Data on dental appliances, oral hygiene/care practices before and during treatment were collected. RESULTS: A total of 116 patients were included (58 RCC treated by sunitinib: group S, and 58 treated by chemotherapy: group C). No differences in dental care habits were noted before treatment. In group S, patients reported significantly more frequent pain (P<0.01), teeth instability (P=0.01), gingival bleeding (P=0.01) and change in teeth colour (P=0.02). In all, 58% of patients in this group had to modify their diet (P<0.01). Frequency of dentist visits for teeth removal was increased (25% vs 8%, P=0.01). CONCLUSION: Sunitinib seems to increase buccodental toxicity as compared with chemotherapy. This finding emphasises the need for optimal dental care and standardised dental follow-up in patients treated with sunitinib.

Quality of life in a heterogeneous sample of caregivers of cancer patients: an in-depth interview study.

To establish the best approach to develop a quality of life (QoL) questionnaire for cancer-patient caregivers, this study attempts to identify primary domains of QoL in terms of their impact on a purposive sample of caregivers. Seventy-seven informal adult caregivers of cancer patients (breast cancer, paediatric haematological malignancies or melanoma) with different relationships with the patients (parents, children, spouses, siblings, and friends) were recruited at three specialised French centres and extensively interviewed. Caregivers' lives were altered in several domains: psychological well-being, leisure and everyday activities, relationships with institutional caregivers, occupation and finances, relationships with family and friends, physical well-being, and relationship with the patient. The relative importance of these domains varied mainly in association with the caregiver-patient relationship. Multiple correspondence analysis identified two isolated clusters: children, and, most significantly, friends and siblings. The latter groups emphasised the repercussions on their psychological well-being and their relationship with the patient, but were less willing to discuss the impact on their relationship with caregivers and on occupation, finances, leisure, and everyday activities. This study focuses on the caregiver's perspective and advocates the development of a short QoL core questionnaire. Additional modules should be cancer-specific or dedicated to specifics of the caregiver-patient relationship.

Participants' uptake of clinical trial results: a randomised experiment.

BACKGROUND: Participants are showing great interest these days in obtaining the results of clinical trials. The aim of this study was to assess patients' uptake and understanding of the results of the trial in which they have participated and the impact of a letter offering patients the possibility of consulting the trial results on a specific website. METHODS: Breast cancer patients participating in a trial on the efficacy of Trastuzumab were randomly subdivided into an Internet group (who received the letter of invitation) and a control group (who did not receive it). Among 115 HER2-positive women from 21 centres, 107 (93%) answered a self-administered questionnaire. RESULTS: Most of the patients in both groups had access to the Internet (72.0%). The majority (97.2%) stated that receiving information about the trial results would be useful, and the oncologist was the most frequently preferred information provider. The Internet group's declared uptake of the trial results was only slightly higher (47.1% vs 33.9%; P=0.166); however, they understood the results significantly more accurately (18.8% vs 5.6%; P=0.039). INTERPRETATION: Although Internet was not the respondents' preferred source of information, the possibility of using this source slightly increased the uptake and understanding of the results.

High-dose alkylating agents with autologous hematopoietic stem cell support and trastuzumab in ERBB2 overexpressing metastatic breast cancer: a feasibility study.

BACKGROUND: ERBB2 overexpression predicts a worse outcome for patients receiving high-dose chemotherapy (HDC). Trastuzumab improves response rate and survival in ERBB2 overexpressing metastatic breast cancer patients (MBC). We investigated the feasibility of combining high-dose alkylating agents with autologous hematopoietic stem cell (AHSC) support and trastuzumab in ERBB2 overexpressing MBC. PATIENTS AND METHODS: Eleven consecutive patients with pre-treated ERBB2 overexpressing MBC were enrolled. HDC regimen consisted of a single course of cyclophosphamide 120 mg/kg + melphalan 140 mg/m2 (CyMEL, n =8), a single course of Thiotepa 600 mg/m2 (TTP, n = 1) or a sequential combination of Thiotepa 600 mg/m2 followed on day 21 by BCNU 600 mg/m2 (TTP-BCNU, n =2). Trastuzumab (4mg/kg) was started 24 h after AHSC infusion and then administered weekly (2 mg/kg). RESULTS: Median time to neutrophil and platelet recovery was 10 and 14.5 days, respectively. Three patients experienced febrile neutropenia and in 2 Herpes virus infections were documented. Five grade III/IV mucositis/oesophagitis were recorded. One patient experienced a reversible atrial arrhythmia on day 2 of trastuzumab, and another patients had a nonsymptomatic decrease in LVEF >10% on week 12 of trastuzumab. No toxic death was recorded. Median time to progression was 5 months (1 to 38 +). CONCLUSION: Combining alkylating agent-based HDC and trastuzumab appears to be feasible in ERBB2 overexpressing MBC and warrants further investigation in a larger cohort.

Multivariate analysis of survival in inflammatory breast cancer: impact of intensity of chemotherapy in multimodality treatment.

The prognosis of inflammatory breast cancer (IBC) is poor. We evaluated clinical and biopathological characteristics that could affect survival in 74 women with nonmetastatic IBC consecutively treated in our institution between 1976 and 2000. Patients received primary anthracycline-based chemotherapy at conventional doses (n=20) or high-dose chemotherapy (HDC) with haematopoietic stem cell support (HSCS) (n=54). After chemotherapy, 84% of patients underwent mastectomy, 95% were given radiotherapy and 55% tamoxifen. Immunohistochemistry data (ER, PR, ERBB2, P53) on pre-chemotherapy specimens suggested strong differences between IBC and non-IBC. The rate of pathological complete response to chemotherapy was 26% (27% with HDC and 17% with conventional doses, not significant). No single factor was found predictive of response. With a median follow-up of 48 months after diagnosis, the 5-year projected disease-free survival (DFS) was 24% and overall survival (OS) 41%. In multivariate analysis, the strongest independent prognostic factor was the delivery of HDC. The 5-year DFS and OS of patients were respectively 28 and 50% with HDC and 15 and 18% with conventional chemotherapy. These results and comparisons with other series of patients suggest a role for HDC with HSCS as part of the therapeutic approach in IBC. Further prospective studies are required to confirm it.

Phase I study of pegylated liposomal doxorubicin (Caelyx) in combination with carboplatin in patients with advanced solid tumors.

PURPOSE: To determine the maximum tolerated dose of the combination of Carboplatin and Caelyx, a pegylated liposomal doxorubicin, with promising activities in various solid tumors. PATIENTS AND METHODS: Twenty-two patients with various advanced solid tumors were included. Three dose levels of Caelyx were explored: 30, 35 and 40 mg/m2 in association with a fixed dose of Carboplatin (AUC 5) every 3 weeks. Dose escalation followed a modified continuous reassessment method. RESULTS: Dose-limiting toxicities were almost exclusively hematological: 3 febrile neutropenia, 1 grade 4 neutropenia lasting more than 7 days and 2 grade 4 thrombopenia were observed. Grade 4 neutropenia and febrile neutropenia were observed in 20 and 10% of courses, respectively. The median interval between courses was 25 days after cycle 1 and 27-28 days after subsequent cycles. Palmar-plantar erythrodysesthesia, mucositis and other non hematological toxicities were mild and uncommon. One patient experienced a severe anaphylactic reaction immediately after Caelyx infusion. No clinical heart dysfunction was observed. Three patients responded to therapy including 2 clinical complete responses in relapsing ovarian cancer. CONCLUSION: The recommended dose for future studies is Caelyx 35 mg/m2 + Carboplatin AUC 5 every 3 or 4 weeks. Antitumor activity, especially in ovarian cancer, warrants further investigation in phase II studies.